GI-Pharmacology (USMLE)

List 2 disorders associated with gastroparesis.
diabetes

Parkinson’s disease

* post-surgical, idiopathic

List 3/6 symptoms of gastroparesis
abdominal distension

hypoglycemia (diabetes)

nausea

premature fullness while eating a meal

weight loss without trying

vomiting

What 3 receptors are acted upon by metoclopramide?
D2 antagonist

5-HT3 antagonist

5-HT4 agonist

Which 2 receptors mediates the anti-emetic actions of metoclopramide?
D2 antagonist in the chemoreceptor trigger zone in the CNS

5-HT3 antagonist

Which receptor mediates the prokinetic actions of metoclopramide?
5-HT4 agonist

What neurological disorder may be worsened with use of metoclopramide?
Parkinson’s disease (dopamine antagonist)

*CONTRAINDICATED

Metoclopramide uses (3)
diabetic gastroparesis

anti-emetic

GERD (not preferred drug)

How does cisapride affect the following?

myenteric plexus

muscle tone in esophageal sphincter

release Ach in myenteric plexus

increases muscle tone in the esophageal sphincter

Cisapride uses (3)
GERD

gastric emptying in diabetic gastroparesis

bowel constipation

Cisapride adverse effect
long QT syndrome

List 3/5 types of medication that can cause constipation.
opioids

diuretics

antispasmodics

antidepressants

antihistamines

List 3/6 diseases that can cause constipation.
hypothyroidism

irritable bowel syndrome

hypercalcemia

diabetes mellitus

cystic fibrosis

Parkinson’s disease

Senna MOA
stimulant laxative

* evacuation of bowels within 8-10 hours

What stool softener is often administered alongside senna?
docusate (+sodium, calcium, potassium)

*surface active agents emulsified with stools to make softer and easy passage

Which 2 drug combination is used to treat opioid-induced constipation?
senna + docusate

Bisacodyl MOA
potent stimulant of the colon that acts directly on the nerve fibers in the mucosa of the colon

Bisacodyl adverse effects (2)
abdominal cramps

atonic colon

Which laxative can cause atonic clonic with prolonged use?
bisacodyl

Why should antacids not be taken at the same time with enteric-coated tablets such as bisacodyl?
cause enteric coating to dissolve too early in the stomach, resulting in stomach irritation and pain

*H2 blockers and proton pump inhibitors

Castor oil MOA
irritant laxative

What acid is derived from castor oil?
ricinoleic acid

Castor oil contraindication
pregnancy

* stimulates uterine contractions

What type of laxatives form gels in the large intestine, causing water retention and intestinal distension, thus increasing peristaltic activity?
bulk laxatives

List 3 laxatives that have actions similar to bulk laxatives.
methylcellulose

psyllium seeds

bran

What complication is associated with bulk laxatives in bed-bound patients?
intestinal obstruction

List 4 nonabsorbable salts that hold water in the intestine by osmosis and distend the bowel, causing stimulation followed by defecation.
magnesium citrate

magnesium sulfate

magnesium phosphate

magnesium hydroxide

Semi-synthetic dissaccharide sugar that acts as an osmotic laxative
lactulose

* large doses degraded by colonic acid to form lactic, formic, and acetic acid

Name an osmotic laxative used for colonic lavage for endoscopic and radiological procedures.
polyethylene glycol

List 2 lubricant laxatives.
mineral oils and glycerin suppositories

Draw the emesis pathway. List the 4 centers that act on the vomiting center in the medulla.
Draw the emesis pathway. List the 4 centers that act on the vomiting center in the medulla.

List 5 receptors associated with the chemoreceptor trigger zone.
D2

5-HT3

opioid

Ach

substance P

List 2 receptors in the labyrinths that mediate emesis.
muscarinic

H1

What receptor in the stomach and small intestine mediate emesis?
5-HT3

* activated by GI distension or acute GI infections

Which vomiting center responds directly to chemical stimuli in the blood or cerebrospinal fluid?
chemoreceptor trigger zone

Which part of the brainstem coordinates the motor mechanisms of vomiting?
medulla

Which system is involved in emesis due to motion sickness?
vestibular system

Which anticholinergic drug can be used to treat motion sickness?
scopolamine

* muscarinic blocker

List 3 H1 blockers used to treat motion sickness.
dimenhydrinate

meclizine

cyclizine

Prochlorperazine MOA
D2 blocker

What phenothiazine is effective against low or moderately emetogenic chemotherapeutic agents such as fluorouracil and doxorubicin?
prochlorperazine

* D2 blocker

Which antiemetic drug can cause hypotension and restlessness?
prochlorperazine

Which antiemetic phenothiazine can cause extrapyramidal symptoms and sedation?
prochlorperazine

Ondansetron MOA
5-HT3 blocker

* periphery (visceral vagal afferent fibers)
* brain (chemoreceptor trigger zone)

Granisetron MOA
5-HT3 blocker

* periphery (visceral vagal afferent fibers)
* brain (chemoreceptor trigger zone)

Which antiemetics (based on mechanism) are administered prior to chemotherapy?
5-HT3 blockers

*ondansetron, granisetron, dolasetron

Which 5-HT3 blocker can cause prolongation of the QT interval?
dolasetron

Which antiemetic drug is effective at high doses against the highly emetogenic cisplatin?
metoclopramide

Metoclopramide adverse effects (4/7)
sedation

restlessness

fatigue

depression

nausea

diarrhea

extrapyramidal symptoms: tardive dyskinesia

Butyrophenones MOA
D2 blockers

Which butyrophenone can prolong the QT interval?
droperidol

List the 2 butyrophenones.
droperidol

haloperidol

List 2 benzodiazepines used as antiemetics.
lorazepam

alprazolam

* potency low
* beneficial effects due to sedative, anxiolytic, and amnesic properties
* useful in anticipatory vomiting

List 2 corticosteroids used as antiemetics.
dexamethasone

methylprednisolone

* antiemetic mechanism not known; maybe blockade of prostaglandins

Which antiemetic drugs are associated with insomnia and hyperglycemia?
corticosteroids

List 2 marijuana derivatives used as antiemetics.
dronabinol

nabilone

Which antiemetics are associated with dysphoria, hallucinations, sedation, vertigo, and disorientation?
marijuana derivatives

* dronabinol, nabilone
* not first-line antiemetics
* effective in mild to moderate emesis (chemotherapy induced)

Aprepitant MOA
neurokinin-1 (substance P) blocker

List 2 drugs often administered along with aprepitant.
dexamethasone

palonosetron

Which CYP 450 enzyme metabolizes aprepitant?
CYP 3A4

* can also induce enzyme and shorten half-life of warfarin

Which antiemetic drug can cause constipation and fatigue?
aprepitant

List 2 emetics used in accidental poisoning.
apomorphine

syrup ipecac

3 or more unusually frequent soft or liquid bowel movements
diarrhea

List 2 antidiarrheals that activate presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis.
diphenoxylate

loperamide

Why is atropine administered with the antidiarrheal diphenoxylate?
discourage abuse

Which 2 antidiarrheals are associated with toxic megacolon in young children or in patients with severe colitis?
diphenoxylate

loperamide

List 2 antidiarrheals that are associated with drowsiness, abdominal cramps, and dizziness.
diphenoxylate

loperamide

Name an antidiarrheal that is a long-acting somatostatin derivative.
octreotide

Name an antidiarrheal approved for the control of diarrheas associated with metastatic carcinoid tumors and vasoactive intestinal peptide tumors.
octreotide

Which antidiarrheal coats the intestinal epithelium to decrease GI irritation?
bismuth subsalicylate

Which inflammatory bowel disease is associated with “skip lesions?”
Crohn’s disease

* can involve any part of GIT from mouth to anus

What part of the GIT is most commonly affected in Crohn’s disease?
terminal ileum

* extra-intestinal manifestations include arthritis, skin rashes, eye lesions, and liver problems

Which inflammatory bowel disease is limited to the colon and rectum?
ulcerative colitis

List 3 complications leading to fatalities in inflammatory bowel disease.
toxic megacolon

bowel perforation

colorectal cancer

Drug of choice in acute cases of inflammatory bowel disease.
steroids

* glucocorticoids, prednisone, prenisolone
* methotrexate and 6-mercaptopurine also used

List a sulfonamide derivative used to treat inflammatory bowel disease.
sulfasalazine

List 2 derivatives of sulfasalazine.
sulfapyridine (antibacterial)

5-aminosalicylic acid (anti-inflammatory)

*activated by colonic bacteria

List 3 preparations of 5-aminosalicylic acid.
pentasa

asacol

olsalazine

* used to maintain inflammatory bowel disease remission

List a monoclonal antibody against cellular adhesion molecule of alpha4-integrin that can be used in inflammatory bowel disorders.
natalizumab

Functional bowel disorder characterized by mild to severe abdominal pain, discomfort, bloating, and alteration of bowel habits
irritable bowel syndrome

*exclude the following:*
– parasitic infections
– lactose intolerance
– small intestinal bacterial overgrowth
– celiac disease

List 3 drugs used in irritable bowel syndrome-C that help avoid “cathartic colon.”
polyethylene glycol

sorbitol

lactulose

*cathartic colon*: damage to the nerves of the colon due to excessive use of stimulant laxatives

Describe how the following present in *Reye’s syndrome.*

liver

blood glucose

CNS

fatty liver

hypoglycemia

coma

What drug is associated with Reye’s syndrome?
aspirin

acetaminophen may be advised in place of aspirin

What enzyme secreted from the duodenal mucosa converts trypsinogen to trypsin?
enterokinase/enteropeptidase

What drug dissolves gallstones in the bile ducts?
ursodiol (ursodeoxycholic acid)

one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria

Which 1/3 of the esophagus is most commonly affected by GERD?
lower 1/3

– untreated cases can progress to Barret’s esophagus and then adenocarcinoma

GERD etiology (3)
GERD etiology (3)
lifestyle (alcohol, physical inactivity)

hiatal hernia

decreased tone of the lower esophageal sphincter

What type of ulcers are associated with severe head injuries?
Cushing’s stress ulcers

What type of ulcers are associated with burns?
Curling’s stress ulcers

List 3 types of drugs that reduce gastric acid secretion.
H2 blockers

proton pump inhibitors

muscarinic antagonists

What type of drugs improve mucosal defenses in the treatment of peptic ulcer disease?
cytoprotective agents

Describe antacids in terms of

strong/weak

acid/base

weak bases

At what pH is pepsin inactivated?
pH > 4

List 3 commonly used antacids.
aluminum hydroxide

magnesium hydroxide AKA milk of magnesia

calcium carbonate (Tums)

Name the antacids associated with the following adverse effects:

constipation

dense fecal matter formation

diarrhea

nephrolithiasis
Name the antacids associated with the following adverse effects:

constipation

dense fecal matter formation

diarrhea

nephrolithiasis

constipation: aluminum hydroxide

dense fecal matter formation: calcium carbonate

diarrhea: magnesium hydroxide
* Mg2+ poorly absorbed, leading to diarrhea

nephrolithiasis: calcium carbonate

Which antacid can reduce the bioavailability of tetracycline, digoxin, and antimuscarinic drugs?
aluminum hydroxide

Which antacid can reduce absorption of digoxin and tetracycline?
magnesium hydroxide

*due to increased motility (diarrhea)

Which antacid can be given as an adjuvant in the treatment of osteoporosis?
calcium carbonate

List 3 compounds that are important stimuli for the gastric acid secretion from parietal cells. What membrane channel/pump is the final effector of these compounds?
List 3 compounds that are important stimuli for the gastric acid secretion from parietal cells. What membrane channel/pump is the final effector of these compounds?
histamine

acetylcholine
* no significant therapeutic advantage
* not used clinically

gastrin

—–

H+/K+ ATPase pump

Treatment of choice for H. pylori infection
antibiotics

Pirenzepine MOA
Pirenzepine MOA
M1 blocker

H2 receptor G protein
H2 receptor G protein
Gs

Prostaglandin E2 receptor G protein
Prostaglandin E2 receptor G protein
Gi

Which H2 blocker can inhibit CYP-450 enzymes?
Which H2 blocker can inhibit CYP-450 enzymes?
cimetidine

Treatment of choice for GERD
Treatment of choice for GERD
proton pump inhibitor

+/- H2 blocker
* 50% do not find benefit

List 4 H2 blockers.
cimetidine (Tagamet)

nizatidine (Axid)

ranitidine (Zantac)
* 5-10x cimetidine

famotidine (Pepcid)
* 3-20x ranitidine

Treatment of choice for NSAID-induced ulcers
Treatment of choice for NSAID-induced ulcers
proton pump inhibitors

* H2 blockers not effective

What drug is administered IV to high-risk patients in intensive care units to prevent acute stress ulcers?
H2 blockers

Why are H2 blockers administered to preoperative patients?
prevent aspiration pneumonia

What end organ failure leads to increased cimetidine?
renal failure

* 70% excreted unchanged in urine

Which H2 blocker does not produce the antiandrogenic or prolactin-stimulating effects of other H2 blockers?
Which H2 blocker does not produce the antiandrogenic or prolactin-stimulating effects of other H2 blockers?
ranitidine

Which H2 blocker does not have an intravenous preparation?
Which H2 blocker does not have an intravenous preparation?
nizatidine

Which H2 blocker does not have a first-pass metabolism?
Which H2 blocker does not have a first-pass metabolism?
nizatidine

* 100% bioavailability

Which H2 blocker can cross the BBB (confusion, dizziness, headaches) and placenta?
cimetidine

An elderly patient with GERD experiences confusion and hallucinations after intravenous administration of a drug.
H2 blockers

* all except nizatidine

Which H2 blocker is associated with antiandrogenic effects?
cimetidine

*gynecomastia, galactorrhea (prolactin release), and reduced sperm count in men

Which antifungal that depends on a gastric acid medium may not be efficiently absorbed if taken with an H2 blocker?
ketoconazole

What type of ulcers are associated with pain upon food intake?
stomach ulcer

* patient avoids food and experiences weight loss

What type of ulcers are associated with relief upon food intake?
duodenal ulcers

* weight gain

Omeprazole MOA
Omeprazole MOA
proton pump inhibitor (irreversible)

* H+/K+-ATPase

Esomeprazole MOA
Esomeprazole MOA
proton pump inhibitor (irreversible)

* H+/K+-ATPase

In what part of the GI is the acid-resistant enteric coating of proton pump inhibitors removed?
alkaline duodenum

* prodrug, weak base, absorbed and transported to parietal cell canaliculus

With which amino acid residue of the H+/K+-ATPase do proton pump inhibitors form a stable covalent bond?
cysteine residue

DOC for erosive esophagitis
DOC for erosive esophagitis
proton pump inhibitors

DOC for active duodenal ulcers
DOC for active duodenal ulcers
proton pump inhibitors

DOC for Zollinger-Ellison syndrome
DOC for Zollinger-Ellison syndrome
proton pump inhibitors

Which drugs are effective in treating hemorrhagic ulcers because they support platelet aggregation and maintain clot integrity?
Which drugs are effective in treating hemorrhagic ulcers because they support platelet aggregation and maintain clot integrity?
proton pump inhibitors

Omeprazole inhibits the metabolism of which 4 drugs?
warfarin

phenytoin

diazepam

cyclosporine

Prolonged therapy use of proton pump inhibitors and H2 blockers may decrease the bioavailability of which 3 drugs?
vitamin B12

digoxin

ketoconazole

* acid required for absorption

Why is calcium citrate, rather than calcium carbonate, administered to patients taking proton pump inhibitors and/or H2 blockers?
calcium carbonate requires low gastric pH to be absorbed in the upper intestine

Which GI drugs can rarely cause pancreatitis, hepatotoxicity, and interstitial nephritis?
Which GI drugs can rarely cause pancreatitis, hepatotoxicity, and interstitial nephritis?
proton pump inhibitors

Complex of aluminum hydroxide and sulfated sucrose
sucralfate

Sucralfate MOA
binds to proteins at ulcer base

forms complex gels with epithelial cells

physical barrier against HCl

prevents degradation of mucus by pepsin and acid

allows HCO3- secretion to reestablish pH gradient in mucosal layer

What 2 compounds make up sucralfate?
aluminum hydroxide

sulfated sucrose

Why should sucralfate not be administered to patients taking H2 blockers or other antacids?
requires acidic pH for polymerization

How does sucralfate affect the following:

prostaglandin release

mucus output

bicarbonate output

stimulates them all

How does bismuth subsalicylate affect the following:

pepsin activity

mucus secretion

inhibits pepsin activity

increases mucus secretion

* interact with glycoproteins in necrotic mucosal tissue to coat and protect ulcer crater
* does not neutralize stomach acid

Which prostaglandin inhibits secretion of HCl?
PGE2

Describe 2 secretions induced by prostaglandins (PGE2) that bring about a cytoprotective effect on the gastric mucosa.
mucus

bicarbonate

Misoprostol is an analog of which prostaglandin?
PGE1

Which prostaglandin analog can be used to prevent gastric ulcers induced by NSAIDs?
misoprostol

*less effective than H2 blockers and proton pump inhibitors for acute treatment of peptic ulcers

Misoprostol contraindication
pregnancy (women of childbearing potential)

*produces uterine contractions → abortifacient

Misoprostol adverse effects on the GI (2)
diarrhea

nausea

*dose-related

Which anticholinergic agent used in the treatment of peptic ulcers has minimal CNS toxicity due to poor penetration through the blood-brain barrier?
pirenzepine

Dicyclomine MOA
anticholinergic (muscarinic blocker)

* binds to mAChRs in parietal cells
* not as effective as H2 blockers or proton pump inhibitors

What type of ulcers can be treated using anticholinergics?
peptic ulcers

What type of drugs used to treat peptic ulcers can cause arrhythmias and constipation at high doses?
anticholinergics (muscarinic antagonists)

List 3 approaches towards diagnosis of H. pylori infection.
List 3 approaches towards diagnosis of H. pylori infection.
endoscopic biopsy of the gastric mucosa

serologic tests

urea breath test

List 3 first-line regimens for H. pylori eradication.
List 3 first-line regimens for H. pylori eradication.
proton pump inhibitor + clarithromycin + amoxicillin

proton pump inhibitor + clarithromycin + metronidazole

bismuth subsalicylate + metronidazole + tetracycline + ranitidine or proton pump inhibitor

What prokinetic agent can be used as an adjunct to acid-suppressive therapy in the treatment of GERD?
metoclopramide

*not effective in patients with erosive esophagitis

Which 2 H2 blockers decrease renal excretion of creatinine?
cimetidine

ranitiidne

*other H2 blockers relatively free of these effects

Sucaralfate use (2)
increase ulcer healing

traveler’s diarrhea

What prostaglandin analog is used for maintenance of a patent ductus arteriosus?
misoprostol

Name an antidiarrheal approved for the control of acute variceal bleeds.
octreotide

*also used for acromegaly

Octreotide toxicity (3)
nausea

cramps

steatorrhea

Which antacid can cause constipation, hypophosphatemia, proximal muscle weakness, osteodystrophy, and seizures?
aluminum hydroxide

Alumininimum amount of feces

Which antacid can cause diarrhea, hyporeflexia, hypotension, and cardiac arrest?
magnesium hydroxide

Mg = Must go to the bathroom

Which antacid can cause rebound acid increase?
calcium carbonate

*also hypercalcemia

What electrolyte disturbance is associated with all antacids?
hypokalemia

List 4 oxmotic laxatives.
magnesium hydroxide

magnesium citrate

polyethylene glycol

lactulose

Which osmotic laxative can be used to treat hepatic encephalopathy?
lactulose

*gut flora degrades lactulose into metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4+

Osmotic laxatives toxicity (2)
diarrhea

dehydration

What GI disorder is treated using infliximab?
Crohn’s disease

*also rheumatoid arthritis
*monoclonal antibody to TNF

Infliximab toxicity (2)
infection (including reactivation of latent TB

fever

hypotension

Sulfasalazine toxicity (3/4)
malaise

nausea

sulfonamide toxicity

reversible oligospermia

Ondansetron toxicity (2)
headache

constipation

Metoclopramide contraindications (2)
small bowel obstruction

Parkinson’s disease

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*Drugs for GERD and Ulcers*: Drugs that block gastric acid 1) H2 blockers 2) Anticholinergic drugs 3) Prostaglandin analogues 4) Proton pump inhibitors Other: Digestive aids, pepto-bismol, anti-nausea 1) Histamine (H2) Receptor blockers *Cimetidine* -histamine increases gastric acid release. -blocking …

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Aluminum Hydroxide + Magnesium Hydroxide diahrea + constipation = normal poop Magnesium Products/ Reactions Milk of Magnesium -hydroxide Mag- Ox- oxide adverse reactions: Diahrea Hypokalemia Hypermagnesia

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